UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France.
J Virol. 2012 Feb;86(4):2056-66. doi: 10.1128/JVI.06532-11. Epub 2011 Dec 7.
The dynamics of the circulation and distribution of transmissible spongiform encephalopathy (TSE) agents in the blood of infected individuals remain largely unknown. This clearly limits the understanding of the role of blood in TSE pathogenesis and the development of a reliable TSE blood detection assay. Using two distinct sheep scrapie models and blood transfusion, this work demonstrates the occurrence of a very early and persistent prionemia. This ability to transmit disease by blood transfusion was correlated with the presence of infectivity in white blood cells (WBC) and peripheral blood mononucleated cells (PBMC) as detected by bioassay in mice overexpressing the ovine prion protein PrP (tg338 mice) and with the identification of abnormal PrP in WBC after using protein misfolding cyclic amplification (PMCA). Platelets and a large variety of leukocyte subpopulations also were shown to be infectious. The use of endpoint titration in tg338 mice indicated that the infectivity in WBC (per ml of blood) was 10(6.5)-fold lower than that in 1 g of posterior brainstem sample. In both WBC and brainstem, infectivity displayed similar resistance to PK digestion. The data strongly support the concept that WBC are an accurate target for reliable TSE detection by PMCA. The presence of infectivity in short-life-span blood cellular elements raises the question of the origin of prionemia.
传染性海绵状脑病（TSE）病原体在感染个体血液中的循环和分布动力学在很大程度上仍不清楚。这显然限制了对血液在 TSE 发病机制中的作用以及可靠的 TSE 血液检测方法的开发的理解。本研究使用两种不同的绵羊瘙痒病模型和输血，证明了非常早期和持续的朊病毒血症的发生。这种通过输血传播疾病的能力与在过度表达绵羊朊蛋白 PrP（tg338 小鼠）的小鼠中通过生物测定法检测到白细胞（WBC）和外周血单核细胞（PBMC）中存在感染性以及使用错误折叠循环扩增（PMCA）后在 WBC 中鉴定到异常 PrP 相关。血小板和各种白细胞亚群也被证明具有感染性。在 tg338 小鼠中使用终点滴定法表明，WBC（每毫升血液）中的感染性比 1 克后脑干样本低 10（6.5）倍。在 WBC 和脑干中，感染性对 PK 消化显示出相似的抗性。这些数据强烈支持这样的概念，即 WBC 是通过 PMCA 进行可靠 TSE 检测的准确靶标。在寿命短的血液细胞成分中存在感染性引发了关于朊病毒血症起源的问题。
